Myocardial Energy Metabolism in Non-ischemic Cardiomyopathy

Abstract

As the most metabolically demanding organ in the body, the heart must generate massive amounts of energy adenosine triphosphate (ATP) from the oxidation of fatty acids, carbohydrates and other fuels (e.g., amino acids, ketone bodies), in order to sustain constant contractile function. While the healthy mature heart acts omnivorously and is highly flexible in its ability to utilize the numerous fuel sources delivered to it through its coronary circulation, the heart's ability to produce ATP from these fuel sources becomes perturbed in numerous cardiovascular disorders. This includes ischemic heart disease and myocardial infarction, as well as in various cardiomyopathies that often precede the development of overt heart failure. We herein will provide an overview of myocardial energy metabolism in the healthy heart, while describing the numerous perturbations that take place in various non-ischemic cardiomyopathies such as hypertrophic cardiomyopathy, diabetic cardiomyopathy, arrhythmogenic cardiomyopathy, and the cardiomyopathy associated with the rare genetic disease, Barth Syndrome. Based on preclinical evidence where optimizing myocardial energy metabolism has been shown to attenuate cardiac dysfunction, we will discuss the feasibility of myocardial energetics optimization as an approach to treat the cardiac pathology associated with these various non-ischemic cardiomyopathies.

NMR-Based Metabolomic Analysis of Sera in Mouse Models of CVB3-Induced Viral Myocarditis and Dilated Cardiomyopathy

“…It was previously reported that cardiac mitochondrial oxidative metabolism and glucose oxidation are suppressed in an energy starved heart in cardiomyopathy and heart failure [ 32 ]. Thus, the up-regulated level of 3-HB might be an adaptive response to lessen the severity of heart failure and increase energy supply in cardiomyopathy [ 32 , 33 ].…”

The Association between the Clinical Severity of Heart Failure and Docosahexaenoic Acid Accumulation in Hypertrophic Cardiomyopathy

“…The remaining ATP is produced through aerobic glycolysis. [3] In normal hearts, FAs account for the majority of oxidative metabolism. However, in hypertrophied hearts, FA oxidation is reduced and glucose utilization is increased.…”

“…In terms of cell metabolism, hypertrophied myocardium requires a large amount of energy, and often presents with relative myocardial ischemia, irrespective of the presence of gene mutations. [2,3] In HCM with HF, metabolic disproportion is likely to occur. [4] This abnormal energy metabolism in HCM has long been clinically con rmed by positron emission tomography-computed tomography as a hyperglycemic state.…”

Ketogenic Diet and Health

“…Traditionally, pharmacological interventions target neurohormonal axes and hemodynamic disturbances. However, emerging evidence suggests the possibility that ketone metabolic modulation might become a viable treatment paradigm for HF [137,139]. Recent studies indicate that enhanced myocardial ketone use is adaptive in HF, and limited data demonstrate beneficial effects of exogenous ketone therapy in studies of animal models [140] and humans with HF [138,[140][141][142][143][144][145][146].…”